Angiogenesis is an essential component of wound healing regardless if the wound is traumatic or surgical in origin. Angiogenesis is also a component of several pathologic conditions, such as the growth of tumors, diabetic retinopathy and arthritis, as well as a component of normal growth and development. The initiation and regulation of these angiogenic processes is not fully understood nor likely to be the same in each case. Macrophages are essential to wound healing and may be the only inflammatory cells capable of expressing an angiogenesis factor. This proposal will concentrate on the functional and structural characterization of an angiogenesis factor secreted by primary rabbit macrophages and to determine how that factor relates both functionally and structurally to an angiogenesis factor derived from human wound fluid. If there is more than one angiogenesis factor derived from macrophages or wounds, then the specific goal of this proposal is to study the nonmitogenic macrophage/wound fluid angiogenesis factor. To understand the function of macrophage angiogenesis factor, the response of capillary endothelial cells to the factor must be studied. An angiogenic response can be divided into three phases, production of proteinases, migration, and proliferation. Because macrophage angiogenesis factor is not mitogenic, the major effort of this investigation will focus on proteinase induction and cell migration. These studies will provide insights into the role of macrophage mediated angiogenesis during wound healing. This information may also be pertinent to an understanding of angiogenesis that may result from pathologic inflammation.